Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Objective: To evaluate the therapeutic potential and underlying mechanisms of action of propolis in db/db mice. Methods: The chemical composition of propolis was analyzed using UHPLC-MS/MS. Thirty mice, including six wt/wt and 24 db/db mice, were randomly assigned to four groups (n = 6 per group): control, model, metformin (250 mg/kg), low dose propolis (100 mg/kg), and high dose propolis (HDP; 400 mg/kg). Treatments were administered orally for four weeks. Body weight and FBG levels were recorded weekly, and an oral glucose tolerance test was conducted on the 25th day. Serum levels of FIN, GSP, connecting peptide, AST, ALT, HDL, LDL, TG, and TC were quantified using ELISA. Liver histopathology was assessed using H&E and PAS staining. Western blotting was performed to examine the expression levels of NF-κB, phosphorylated NF-κB, IκBα, pIκBα, and AKT in liver tissues. Results: The top 10 metabolites of propolis were identified in positive and negative ion modes. The HDP group exhibited a significant reduction in FBG levels, body weight, connecting peptide levels, homeostatic model assessment of β-cell function scores, and homeostasis model assessment of insulin resistance scores (all P < .05). GSP levels were significantly reduced in both treatment groups (all P < .001). The HDP group also exhibited a reduction in TC and LDL levels (both P < .05), whereas HDL levels increased in both treatment groups (all P < .05). Liver weight, AST levels, and ALT levels were reduced in both treatment groups (all P < .05). Histological analysis revealed improved liver morphology. Protein analysis demonstrated downregulation of phosphorylated NF-κB and phosphorylated IκB, alongside upregulation of AKT. Conclusion Propolis exhibited significant antihyperglycemic effects in db/db mice, potentially by modulating the AKT and NF-κB signaling pathways, highlighting its potential as a therapeutic agent for diabetes management.

Objective To investigate the current situation of emergency response management during new outbreaks of infectious diseases in central sterile supply department(CSSD)of hospitals in 18 provinces(autonomous regions and municipalities),and to provide a reference basis for the establishment of a sound emergency response management system.Methods A convenience sampling method was used to investigate and study the CSSDs in 447 hospitals from June to December 2023 using a self-developed questionnaire.The questionnaire included 3 aspects,including general information,emergency disposal management situation(including environment management,personnel management,material management,and process management),and satisfaction with emergency disposal management,and the relevant factors affecting the satisfaction with the emergency disposal management of CSSDs responding to new outbreaks of infectious disease devices were analyzed.Results A total of 447 questionnaires were recovered,with 442 valid questionnaires and a valid questionnaire recovery rate of 98.88％.In terms of environmental management,CSSDs in 88(19.91％)hospitals set up independent instrument pre-sterilization rooms for infected device disposal.In terms of material management,CSSDs in 42(9.50％)hospitals conducted daily emergency material management.In terms of personnel management,CSSDs in 236(53.39％)hospitals conducted emergency response knowledge assessments.In terms of process management,CSSDs in 225(50.90％)hospitals conducted information traceability system full-process closed-loop management.The results of multiple linear regression analysis showed that whether or not to carry out pre-treatment,emergency supplies stockpiling and management,emergency disposal knowledge assessment,establishment of standard operating procedures,and full-process closed-loop management of the traceability system were the influencing factors affecting the satisfaction of CSSD's emergency disposal management(P＜0.05).Conclusion The current situation of CSSD's emergency disposal management of new outbreaks of infectious diseases needs to be improved,and the environmental management of the decontamination area should be strengthened to improve the staff's ability of emergency disposal,guarantee the reserve of emergency supplies,and strengthen the informatization of the whole process management,to reduce the risk of hospital infections and safeguard the quality of medical care.

Objective To investigate the current situation of emergency response management during new outbreaks of infectious diseases in central sterile supply department(CSSD)of hospitals in 18 provinces(autonomous regions and municipalities),and to provide a reference basis for the establishment of a sound emergency response management system.Methods A convenience sampling method was used to investigate and study the CSSDs in 447 hospitals from June to December 2023 using a self-developed questionnaire.The questionnaire included 3 aspects,including general information,emergency disposal management situation(including environment management,personnel management,material management,and process management),and satisfaction with emergency disposal management,and the relevant factors affecting the satisfaction with the emergency disposal management of CSSDs responding to new outbreaks of infectious disease devices were analyzed.Results A total of 447 questionnaires were recovered,with 442 valid questionnaires and a valid questionnaire recovery rate of 98.88％.In terms of environmental management,CSSDs in 88(19.91％)hospitals set up independent instrument pre-sterilization rooms for infected device disposal.In terms of material management,CSSDs in 42(9.50％)hospitals conducted daily emergency material management.In terms of personnel management,CSSDs in 236(53.39％)hospitals conducted emergency response knowledge assessments.In terms of process management,CSSDs in 225(50.90％)hospitals conducted information traceability system full-process closed-loop management.The results of multiple linear regression analysis showed that whether or not to carry out pre-treatment,emergency supplies stockpiling and management,emergency disposal knowledge assessment,establishment of standard operating procedures,and full-process closed-loop management of the traceability system were the influencing factors affecting the satisfaction of CSSD's emergency disposal management(P＜0.05).Conclusion The current situation of CSSD's emergency disposal management of new outbreaks of infectious diseases needs to be improved,and the environmental management of the decontamination area should be strengthened to improve the staff's ability of emergency disposal,guarantee the reserve of emergency supplies,and strengthen the informatization of the whole process management,to reduce the risk of hospital infections and safeguard the quality of medical care.

Objective:To investigate the hospitalization utilization of pneumoconiosis patients and its influencing factors in a northwestern city, and to provide theoretical basis for formulating service policies for pneumoconiosis patients.Methods:From March to October 2021. Existing living pneumoconiosis patients in kashgar were selected as the research objects. The "Survey Questionnaire on Medical Behaviors and Influencing Factors of Pneumoconiosis Patients" developed by the National Institute of Occupational Health and Poison Control of China Centers for Disease Control and Prevention was used to collect pneumoconiosis patients infomations from March to October 2021. This study investigated the demographic characteristics of pneumoconiosis patients, the types and stages of pneumoconiosis, as well as hospitalization in the past year, reasons for hospitalization, treatment measures, reasons for discharge. Additionally, it examined factors influencing medical behaviors, including medical insurance reimbursement, work-related injury insurance, and compensation situations.Logistics regression was used to analyze the influencing factors of hospitalization utilization.Results:The average age of the pneumoconiosis patients was elder with the age of 64.8. 86.7% (156/178) of them were retired, 75.8% (135/178) of them relied primarily on pensions for their income. The main types of pneumoconiosis were silicosis and coal workers' pneumoconiosis with the proportion of 57.3% (102/178) and 24.2% (43/178). 67.4% of them were stage I. The hospitalization rate in the year prior to the survey was 37.1%. The factors that promoted hospitalization were pension as the main source of income, pneumoconiosis in stage II, silicosis as the pneumoconiosis type, suffering joint pain, with two OR more other lung diseases (tuberculosis, cor pulmonale, COPD, pulmonary infection, bulla or pneumothorax, lung cancer, or mesothelioma) ( P<0.05) . Conclusion:The hospitalization rate of pneumoconiosis patients in the previous year was low. It is mainly influenced by the patient's economic income, the duration of pneumoconiosis, and the presence of comorbidities.

Objective To explore the potential prognostic factors of patients with acute ischemic stroke(AIS)after undergoing endovascular mechanical thrombectomy and to construct an effective predictive model.Methods A retrospective analysis of clinical data was conducted on 202 patients with anterior circulation large vessel occlusion AIS from 2 stroke centers.All patients received endovascular mechanical thrombectomy treatment,with treatment and follow-up lasting at least 90 d.Basic demographic characteristics,medical records,and baseline blood biomarker data were collected,and the potential prognostic indicators for AIS after 90 d were screened using least absolute shrinkage and selection operator(LASSO)-logistic regression analysis.Results It was found that alcohol drinking(P=0.029),hypertension(P=0.001),diabetes mellitus(P=0.021),stroke or transient ischemic attack(P=0.049),systolic blood pressure on admission(P=0.009),diastolic blood pressure on admission(P=0.038),blood glucose(P=0.003),white blood cell count(P=0.001),neutrophil count(P=0.001),fibrinogen(P=0.010),systemic immune-inflammation index(P=0.008)and neutrophil-to-lymphocyte ratio(NLR)(P＜0.001)were associated with adverse clinical outcomes.Nine significant prognostic determinants were screened through LASSO-logistic regression analysis.Multivariate logistic regression analysis revealed that male sex(P=0.008),smoking history(P=0.013),hypertension(P=0.011),lymphocyte(P=0.028),fibrinogen(P=0.016),and NLR(P＜0.001)were significant predictive factors for poor prognosis in AIS patients after endovascular thrombectomy treatment.The constructed prognostic model had an accuracy of 76.2％,a sensitivity of 78.2％,a specificity of 71.7％,and a positive predictive value of 86.7％.Conclusion The predictive model established in this study can assist clinicians in identifying high-risk patients with AIS who have undergone endovascular thrombectomy,and it provide guidance for formulating individualized treatment strategies.

Objective:To explore the diagnostic value of the macrophage activation syndrome/systemic juvenile idiopathic arthritis（MS）score in macrophage activation syndrome（MAS）associated with systemic juvenile idiopathic arthritis（sJIA），and to provide a reference for clinical work.Methods:This study was a retrospective case-control analysis，conducted on the patients initially diagnosed as sJIA-associated with MAS and admitted into the Department of Rheumatology and Immunology of Children's Hospital Affiliated to Xi 'an Jiaotong University from July 1st，2016 to June 30th，2023. All of the patients met the diagnostic criteria for patients with MAS associated with sJIA according to the 2016 European Alliance of Associations for Rheumatology（EULAR）/American College of Rheumatology（ACR）/Pediatric Rheumatology International Trials Organization（PRINTO）standards. The basic information at baseline，clinical manifestations，and auxiliary examination results were collected. The MS score was applied to re-evaluate the children diagnosed as sJIA-associated with MAS. When the MS score ≥-2.1，the possibility of sJIA with MAS was high. Thirty cases of sJIA without MAS were randomly selected as the control group.Results:There were 28 cases in the MAS group，including 13 males（46.43%）and 15 females（53.57%），with an average age of（7.51±4.01）years. Compared with the control group，the MAS group were significantly more likely to have high fever（ χ2=8.539， P=0.003），hepatomegaly（ χ2=11.621， P<0.001），splenomegaly（ χ2=11.710， P<0.001）and neurological involvement（ χ2=27.619， P<0.001），with the differences being statistically significant. Meanwhile，there were statistically significant differences between the two groups in terms of white blood cell count（ Z=-4.001， P<0.001），neutrophil count（ Z=-3.659， P<0.001），platelet count（ Z=-4.687， P<0.001），albumin level（ Z=-4.018， P<0.001），alanine aminotransferase（ Z=-3.846， P<0.001），aspartate aminotransferase（ Z=-5.932， P<0.001），lactate dehydrogenase（ Z=-6.150， P<0.001），triglycerides（ Z=-5.874， P<0.001），fibrinogen（ Z=-5.808， P<0.001），ferritin（ Z=-5.280， P<0.001），erythrocyte sedimentation rate（ Z=-3.971， P<0.001），ferritin/erythrocyte sedimentation rate（ Z=-5.433， P<0.001），reduction of two-line cells in blood（ χ2=11.408， P<0.001）and the presence of hemophagocytosis in bone marrow smears（ χ2=28.260， P<0.001）. Moreover，there was a statistically significant difference in MS scores between the two groups（ Z=-6.148， P<0.001），with higher MS scores in the MAS group. Nevertheless，this study showed the median MS scores of both groups ≥-2.1. Conclusion:The MS score was significant to a certain degree as reference for the diagnosis of MAS，and this study showed that the MS score in the MAS group was significantly higher than the control group. However，the median MS scores in both groups were no less than -2.1. This might be related to the influence of factors during the assessment，which made it necessary to optimize the cutoff values of the MS score. Therefore，prospective studies should be carried out on the role of MS score in early identification of MAS.

Objective To investigate the relationship between the levels of type Ⅲ procollagen(PCⅢ)and heme-binding protein(HPX)in peripheral blood,blood lipid and liver fibrosis in patients with nonalcoholic steatohepatitis(NASH).Methods Totally 126 patients with NASH admitted to the hospital from January 2021 to December 2023 were selected as NASH group,and they were divided into 3 subgroups according to the degree of liver fibrosis:no liver fibrosis group(22 cases),mild group(63 cases),moderate and severe group(41 cases).In addition,150 healthy subjects in the same period were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect and compare the levels of PC Ⅲ and HPX in periph-eral blood of all groups,and Pearson correlation analysis was used to explore the correlation between peripher-al blood PC Ⅲ and HPX levels and related indexes of blood lipids in NASH patients.The predictive value of peripheral blood PC Ⅲ and HPX for liver fibrosis in NASH patients was evaluated by receiver operating char-acteristic(ROC)curve.Results The levels of PC Ⅲ and HPX,as well as total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in NASH group were higher than those in control group,and the levels of high density lipoprotein cholesterol(HDL-C)were lower than those in control group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that the lev-els of PCⅢ and HPX in peripheral blood of NASH patients were positively correlated with TC,TG and LDL-C(P＜0.05),while negatively correlated with HDL-C(P＜0.05).The levels of PC Ⅲ and HPX in peripheral blood of the non-fibrosis group were lower than those of the mild and moderate severe groups,and the mild group was lower than that of the moderate and severe group,and the differences were statistically significant(P＜0.05).The area under the curve(AUC)of peripheral blood PC Ⅲ and HPX in predicting liver fibrosis in NASH patients were 0.757 and 0.861,respectively,and the cut-off values were 135.51 ng/mL and 804.86 mg/L,respectively.The AUC of the combined prediction for liver fibrosis was 0.905,which was higher than that predicted by the two alone.Conclusion The level of PC Ⅲ and HPX in peripheral blood is closely related to the level of blood lipids and the degree of liver fibrosis in NASH patients,which can be used as potential bi-omarkers to predict liver fibrosis in NASH patients.